The aim of the proposed project is to investigate the effect of morphine on hypothalamic dopamine receptors, and the ability of the peptide Cyclo(Leu-Gly) to alter the effects of morphine. Previous results from our laboratory have indicated that a number of peptides related to MIF (Pro-Leu-Gly-NH2), including Cyclo(Leu-Gly) prevent the development of physical dependence on morphine as measured by withdrawal hypothermia. Furthermore, morphine induced changes in the hypothermic response to apomorphine was blocked by Cyclo(Leu-Gly). In parallel studies the peptide was shown to prevent the increase in striatal dopamine receptor binding induced by morphine in a manner which correlated with the blockade of the morphine-induced shift to the left of the dose response curve for apomorphine to produce stereotypic behavior. Since withdrawal hypothermia is the most consistent sign of physical dependence which is blocked by the peptide, and the regulation of body temperature is thought to be mediated, inpart by hypothalamic dopamine neurons the present study is designed to characterize dopamine binding in hypothalamic tissue, then to evaluate the effects of the peptide as well as morphine on this binding, and to test the interaction of these two compounds on these parameters.